ATP effects on insulin-degrading enzyme are mediated primarily through its triphosphate moiety

ATP effects on insulin-degrading enzyme are mediated primarily through its triphosphate moiety

Autor Song, E. S. Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Fried, M. G. Google Scholar
Wagner, S. L. Google Scholar
Hersh, L. B. Google Scholar
Instituição Univ Kentucky
Universidade Federal de São Paulo (UNIFESP)
Neurogenet Inc
Resumo It has been reported previously that ATP inhibits the insulysin reaction (Camberos, M. C., Perez, A. A., Udrisar, D. P., Wanderley, M. I., and Cresto, J. C. ( 2001) Exp. Biol. Med. 226, 334-341). We report here that with 2-aminobenzoyl-GGFLRKHGQ-ethylenediamine-2,4-dinitrophenyl as substrate, ATP and other nucleotides increase the rate >20-fold in Tris buffer. There is no specificity with respect to the nucleotide; however, ATP is more effective than ADP, which is more effective than AMP. Triphosphate itself was as effective as ATP, indicating it is this moiety that is responsible for activation. the binding of triphosphate was shown to be at a site distinct from the active site, thus acting as a noncompetitive activator. With the physiological substrates insulin and amyloid beta peptide, nucleotides and triphosphate were without effect. However, with small physiological peptides such as bradykinin and dynorphin B-9, ATP and triphosphate increased the rate of hydrolysis similar to10-fold. Triphosphate and ATP shifted the oligomeric state of the enzyme from primarily dimer-tetramers to a monomer. These data suggest the presence of an allosteric regulatory site on insulysin that may shift its specificity toward small peptide substrates.
Idioma Inglês
Data de publicação 2004-12-24
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 279, n. 52, p. 54216-54220, 2004.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Biochemistry Molecular Biology Inc
Extensão 54216-54220
Fonte http://dx.doi.org/10.1074/jbc.M411177200
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000225793600041
Endereço permanente http://repositorio.unifesp.br/handle/11600/28053

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